Work of Four TSRI Scientists Contribute in Science Magazine's
Top-Ten Breakthroughs of Year

The work of four scientists at The Scripps Research Institute (TSRI)
was cited by Science magazine among three of the journal's annual
list of the top-ten breakthroughs of the year. The complete list appears
in the December 20, 2002 issue of Science.

All four scientists are in the Department of Cell Biology at TSRI. In
addition, three of the scientists are members of TSRI's Institute for
Childhood and Neglected Diseases (ICND). The ICND was created to apply
the burgeoning knowledge of genes and their interactions to understand,
address, reduce, and treat specific childhood diseases, early-onset diseases,
and "neglected" diseases, which affect populations primarily in developing
countries.

The four scientists and their breakthroughs are:

Professor Steve Kay for "[work on] a new class of light-responsive
cells in the retinas of mammals." Kay recently demonstrated that the gene
Opn4, which codes for the protein Melanopsin, is the elusive pigment gene
that captures light and keeps your body tuned to a daily cyclecalled
a circadian rhythm. "This is the key protein in the eye that sends signals
to the clock," says Kay.

This research should help in the development of strategies for correcting
sleep disorders, many of which are related to circadian rhythms. Furthermore,
understanding the protein that resets the body's clock should help in
research aimed at countering the most common circadian problemsthe
jet-lag one feels after overseas flights or fatigue when working night
shifts.

Assistant Professor Ardem Patapoutian for discoveries that "helped
explain why spicy food feels hot, and breath mints give the mouth a chill."
Patapoutian identified and isolated a protein, called TRPM8, that mediates
the body's ability to sense cold and menthol through the skin. TRPM8 is
the first cold-sensing molecule that has ever been identified and may
be an important basic target for pain-modulating drugs.

He also identified and cloned the first-known gene that makes skin cells
able to sense warm temperatures by making a membrane protein, called TRPV3,
that opens when it senses a temperature above a certain level and allows
ions to pass through and cause an electrical potential that signals the
brain. "This protein may be an important target for drugs," says Patapoutian,
"because, like other TRP channels, it may be involved in inflammation
and pain-mediation."

Assistant Professor Elizabeth Winzeler and Professor John
Yates, who both contributed research in support of the publication
of "genome sequence drafts for organisms with major agriculture and public
health relevance for the developing world."

Winzeler found a way to use a relatively new but readily available technology
to quickly detect markers in the DNA of the most deadly type of malaria
pathogen. The technology could enable scientists and public health workers
to identify the particular strain of malaria during an outbreak and determine
if it is drug resistant or not. The work should also make it easier to
follow the spread of drug resistance around the world, and to assist health
ministries in countries where malaria is a problem to come up with strategies
to thwart this spread.

"One of the reasons for the resurgence of malaria in Africa and in other
parts of the world is the spread of drug resistance," says Winzeler.

Yates led a large effort to determine the "proteome" of the most deadly
form of the malaria pathogenPlasmodium falciparum. Knowing
which proteins are expressed by Plasmodium falciparum should help
scientists understand how the pathogen causes malaria and, with luck,
how to thwart it. These efforts will pay huge dividends in global healthcare
if even a few of the newly identified proteins lead to the development
of new malaria vaccinesand Yates and his colleagues found more than
2,400 proteins.

"This is the first instance that I know of where these proteomics studies
have gone along side-by-side with the genome sequencing project," he says.